Originally published as JCO Early Release 10.1200/JCO.2008.19.7251 on June 29 2009

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Insulin Resistance and Risk Factors for Cardiovascular Disease in Young Adult Survivors of Childhood Acute Lymphoblastic Leukemia

From the Departments of Pediatrics and Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; Center for Cancer and Blood Disorders, Children's Medical Center Dallas; Departments of Family Medicine, Clinical Sciences, and Internal Medicine and the Donald W. Reynolds Cardiovascular Clinical Research Center and the Center for Human Nutrition at The University of Texas Southwestern Medical Center; The Cooper Institute, Dallas, TX; Pennington Biomedical Research Center, Baton Rouge, LA; Klein Buendel, Inc, Golden, CO; Cincinnati Children's Hospital Medical Center, Cincinnati, OH; and School of Kinesiology and Health Studies, Queen's University, Kingston, Ontario, Canada.

Corresponding author: Kevin C. Oeffinger, MD, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021; e-mail: oeffingk{at}mskcc.org.

Purpose To determine the prevalence of insulin resistance and other risk factors for cardiovascular disease (CVD) in young adult survivors of childhood acute lymphoblastic leukemia (ALL).

Patients and Methods In this cross-sectional evaluation of 118 survivors of childhood ALL (median age, 23.0 years; range, 18 to 37 years), insulin resistance was estimated using the homeostasis model for assessment of insulin resistance (HOMA-IR). Sex-specific comparisons were made with a cohort of 30- to 37-year-old individuals from the same region participating in the Dallas Heart Study (DHS, N = 782). ALL survivors were stratified by treatment with and without cranial radiotherapy (CRT).

Results Female ALL survivors had a significantly higher HOMA-IR (CRT, mean 4.6, 95% CI, 3.6 to 5.7; no CRT, mean 3.3, 95% CI, 2.8 to 3.8) in comparison with DHS women (mean 2.4, 95% CI, 2.2 to 2.7). Eighty percent of women treated with CRT had at least three of six CVD risk factors, and they were significantly more likely to have three or more risk factors compared with DHS women (odds ratio [OR], 5.96; 95% CI, 2.15 to 16.47). Male ALL survivors had a significantly higher HOMA-IR (CRT, mean 4.0, 95% CI, 2.8 to 5.6; no CRT, mean 3.4, 95% CI, 2.9 to 3.9) in comparison with DHS men (mean 2.3, 95% CI, 2.1 to 2.6), but were not more likely to have multiple CVD risk factors.

Conclusion ALL survivors had an increased prevalence of insulin resistance in comparison with a cohort of older individuals from the same community. Importantly, women treated with CRT seem to have an increased prevalence of multiple CVD risk factors, warranting close monitoring and risk-reducing strategies.

Supported by the National Institutes of Health (Grant No. R01-CA-100474), the Howard J. and Dorothy Adleta Foundation, the Donald W. Reynolds Cardiovascular Research Center at Dallas, and the General Clinical Research Center (Grants No. M01-RR-00633 and CTSA UL1-RR-024982).

The funding organizations had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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